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Abstract Limb movement direction can be inferred from local field potentials in motor cortex during movement execution. Yet, it remains unclear to what extent intended hand movements can be predicted from brain activity recorded during movement planning. Here, we set out to probe the directional-tuning of oscillatory features during motor planning and execution, using a machine learning framework on multi-site local field potentials (LFPs) in humans. We recorded intracranial EEG data from implanted epilepsy patients as they performed a four-direction delayed center-out motor task. Fronto-parietal LFP low-frequency power predicted hand-movement direction during planning while execution was largely mediated by higher frequency power and low-frequency phase in motor areas. By contrast, Phase-Amplitude Coupling showed uniform modulations across directions. Finally, multivariate classification led to an increase in overall decoding accuracy (>80%). The novel insights revealed here extend our understanding of the role of neural oscillations in encoding motor plans.

The Attentional Control Theory (ACT) posits that, while trait anxiety may not directly impact performance, it can influence processing efficiency by prompting the use of compensatory mechanisms. The specific nature of these mechanisms, which might be reflective, is not detailed by the ACT. In a study involving 110 students (M = 20.12; SD = 2.10), surveys were administered to assess the students’ metacognitive beliefs, trait anxiety, and emotion regulation strategies (ERSs). The participants engaged in two working memory exercises: the digit span task from the WAIS-IV and an emotional n-back task. The findings indicated that anxiety, metacognitive beliefs, and maladaptive ERSs did not affect task performance but were correlated with increased response times. Several regression analyses demonstrated that a lack of confidence in one’s cognitive abilities and maladaptive ERSs predict higher reaction times (RT) in the n-back task. Additionally, maladaptive ERSs also predict an increased use of strategies in the digit span task. Finally, two mediation analyses revealed that anxiety increases processing efficiency, and this relation is mediated by the use of maladaptive ERSs. These results underscore the importance of the reflective level in mediating the effects of trait anxiety on efficiency. They highlight the necessity of incorporating metacognitive beliefs and maladaptive emotion regulation strategies for a thorough comprehension of the Attentional Control Theory. Recognizing these factors offers valuable perspectives for enhancing cognitive capabilities and fostering academic achievement.

Abstract Introduction Dialectical Behavior Therapy (DBT) has assembled a large body of evidence for the treatment of emotional dysregulation in borderline personality disorder (BPD), but also in other disorders characterized by emotional dysregulation (e.g., bipolar disorder (BD) and ADHD). Standalone skills learning groups address the problem of limited resources in several clinical settings. Furthermore, transdiagnostic skills groups facilitate the recruitment and decrease the scattering of resources in psychiatric settings. However, few studies have focused on the pertinence of transdiagnostic standalone skills groups in naturalistic settings as well as their long-term outcomes. The goal of this study is to assess the impact of participation in a transdiagnostic DBT skills group one year after its completion. Method Transdiagnostic DBT skills training groups were provided for BPD, BD and ADHD patients in a University Psychiatric Department (Strasbourg, France), between 2019 and 2020. They consisted of 16 group sessions of 2.5 h and 3 individual sessions. At 1-year follow-up, ad-hoc questionnaires were proposed to all participants to assess the perceived impacts, the changes in symptomatology, and the maintenance of skills learned. Result 22 of the 31 participants were interviewed at the one-year post-group session (64% BPD, 41% ADHD and 27% BD). 73% participants estimated that group impact was important or very important, 64% stated using the skills learned often or very often, mainly emotion regulation skills. An improvement in emotional instability, substance use, impulsivity and suicidal thoughts was reported by respectively 100%, 91%, 86% and 85% of participants. Quality of life improved according to 90% participants. All patients reported an improvement in suicidality during the post-group year, especially in suicide attempts. Psychotropic medication decreased in 59% of participants. Discussion Our one-year naturalistic study suggests that transdiagnostic DBT skills training groups are promising for the treatment of emotional dysregulation in people with BPD, BD and/or ADHD. The observational design and the lack of control group are the main limitations. Randomized controlled studies are required to confirm the long-term efficacy of transdiagnostic skills learning groups in naturalistic settings.

Abstract Familial hypocholesterolemia, namely abetalipoproteinemia, hypobetalipoproteinemia and chylomicron retention disease (CRD), are rare genetic diseases that cause malnutrition, failure to thrive, growth failure and vitamin E deficiency, as well as other complications. Recently, the gene implicated in CRD was identified. The diagnosis is often delayed because symptoms are nonspecific. Treatment and follow-up remain poorly defined. The aim of this paper is to provide guidelines for the diagnosis, treatment and follow-up of children with CRD based on a literature overview and two pediatric centers 'experience. The diagnosis is based on a history of chronic diarrhea with fat malabsorption and abnormal lipid profile. Upper endoscopy and histology reveal fat-laden enterocytes whereas vitamin E deficiency is invariably present. Creatine kinase (CK) is usually elevated and hepatic steatosis is common. Genotyping identifies the Sar1b gene mutation. Treatment should be aimed at preventing potential complications. Vomiting, diarrhea and abdominal distension improve on a low-long chain fat diet. Failure to thrive is one of the most common initial clinical findings. Neurological and ophthalmologic complications in CRD are less severe than in other types of familial hypocholesterolemia. However, the vitamin E deficiency status plays a pivotal role in preventing neurological complications. Essential fatty acid (EFA) deficiency is especially severe early in life. Recently, increased CK levels and cardiomyopathy have been described in addition to muscular manifestations. Poor mineralization and delayed bone maturation do occur. A moderate degree of macrovesicular steatosis is common, but no cases of steatohepatitis cirrhosis. Besides a low-long chain fat diet made up uniquely of polyunsaturated fatty acids, treatment includes fat-soluble vitamin supplements and large amounts of vitamin E. Despite fat malabsorption and the absence of postprandial chylomicrons, the oral route can prevent neurological complications even though serum levels of vitamin E remain chronically low. Dietary counseling is needed not only to monitor fat intake and improve symptoms, but also to maintain sufficient caloric and EFA intake. Despite a better understanding of the pathogenesis of CRD, the diagnosis and management of the disease remain a challenge for clinicians. The clinical guidelines proposed will helpfully lead to an earlier diagnosis and the prevention of complications.

Abstract Children with progressive familial intrahepatic cholestasis, including bile salt export pump (BSEP) and familial intrahepatic cholestasis–associated protein 1 (FIC1) deficiencies, suffer debilitating cholestatic pruritus that adversely affects growth and quality of life (QoL). Reliance on surgical interventions, including liver transplantation, highlights the unmet therapeutic need. INDIGO was an open‐label, Phase 2, international, long‐term study to assess the efficacy and safety of maralixibat in children with FIC1 or BSEP deficiencies. Thirty‐three patients, ranging from 12 months to 18 years of age, were enrolled. Eight had FIC1 deficiency and 25 had BSEP deficiency. Of the latter, 6 had biallelic, protein truncating mutations (t)‐BSEP, and 19 had ≥ 1 nontruncating mutation (nt)‐BSEP. Patients received maralixibat 266 μg/kg orally, once daily, from baseline to Week 72, with twice‐daily dosing permitted from Week 72. Long‐term efficacy was determined at Week 240. Serum bile acid (sBA) response (reduction in sBAs of > 75% from baseline or concentrations 5 years. No patients with FIC1 deficiency or t‐BSEP deficiency met the sBA responder criteria during the study. Maralixibat was generally well‐tolerated throughout the study. Conclusion: Response to maralixibat was dependent on progressive familial intrahepatic cholestasis subtype, and 6 of 19 patients with nt‐BSEP experienced rapid and sustained reductions in sBA levels. The 7 responders survived with native liver and experienced clinically significant reductions in pruritus and meaningful improvements in growth and QoL. Maralixibat may represent a well‐tolerated alternative to surgical intervention.

Introduction Wilson’s disease (WD) is a copper metabolism disorder characterised by a progressive accumulation of this metal mainly in the liver and the brain. Treatment is based on the removal of copper operated by the chelators, among which, D-penicillamine (DP) is prescribed as a first-line treatment in most situations. There is some evidence in linking the use of DP with a risk of vitamin B6; therefore, vitamin supplementation is sometimes recommended, although non-consensually. The objective of our study was to evaluate the level of vitamin B6 in WD patients treated with DP with and without associated supplementation.Methodology All WD patients followed at the National Reference Centre for WD in Lyon between January 2019 and December 2020 treated with DP for more than 1 year were included and separated in two groups according to vitamin B6 supplementation. The level of vitamin B6 was measured by the determination of pyridoxal phosphate (PLP).Results A total of 37 patients were included. Average age of 23.3±14.8 years, 15 patients with

Background & Aims: PEDFIC 2, an ongoing, open-label, 72-week study, evaluates odevixibat, an ileal bile acid transporter inhibitor, in patients with progressive familial intrahepatic cholestasis. Methods: PEDFIC 2 enrolled and dosed 69 patients across two cohorts; all received odevixibat 120 μg/kg per day. Cohort 1 comprised children from PEDFIC 1, and cohort 2 comprised new patients (any age). We report data through 15 July 2020, with Week 24 of PEDFIC 2 the main time point analysed. This represents up to 48 weeks of cumulative exposure for patients treated with odevixibat from the 24-week PEDFIC 1 study (cohort 1A) and up to 24 weeks of treatment for those who initiated odevixibat in PEDFIC 2 (patients who received placebo in PEDFIC 1 [cohort 1B] or cohort 2 patients). Primary endpoints for this prespecified interim analysis were change from baseline to Weeks 22–24 in serum bile acids (sBAs) and proportion of positive pruritus assessments (≥1-point drop from PEDFIC 2 baseline in pruritus on a 0–4 scale or score ≤1) over the 24-week period. Safety monitoring included evaluating treatment-emergent adverse events (TEAEs). Results: In cohort 1A, mean change from PEDFIC 1 baseline to Weeks 22–24 of PEDFIC 2 in sBAs was -201 μmol/L (p

STAT2 is a transcription factor activated by type I and III IFNs. We report 23 patients with loss-of-function variants causing autosomal recessive (AR) complete STAT2 deficiency. Both cells transfected with mutant STAT2 alleles and the patients’ cells displayed impaired expression of IFN-stimulated genes and impaired control of in vitro viral infections. Clinical manifestations from early childhood onward included severe adverse reaction to live attenuated viral vaccines (LAV) and severe viral infections, particularly critical influenza pneumonia, critical COVID-19 pneumonia, and herpes simplex virus type 1 (HSV-1) encephalitis. The patients displayed various types of hyperinflammation, often triggered by viral infection or after LAV administration, which probably attested to unresolved viral infection in the absence of STAT2-dependent types I and III IFN immunity. Transcriptomic analysis revealed that circulating monocytes, neutrophils, and CD8+ memory T cells contributed to this inflammation. Several patients died from viral infection or heart failure during a febrile illness with no identified etiology. Notably, the highest mortality occurred during early childhood. These findings show that AR complete STAT2 deficiency underlay severe viral diseases and substantially impacts survival.

Trait anxiety, emotion regulation strategies, and metacognitive beliefs influence executive functions (EFs) and academic achievement. This study examines their interplay and impact on academic success. In total, 275 adolescents (10–17 years) and parents completed an online questionnaire assessing trait anxiety, emotion regulation strategies, metacognition, parent-reported behaviors related to executive functioning, and overall school average. Preliminary analyses confirmed consistency with the existing literature for each variable and their interaction. Furthermore, we conducted a network analysis among the main variables. This analysis supports the need to pay more attention to reflective variables—maladaptive emotion regulation strategies and metacognitive beliefs about worry—when studying trait anxiety. These variables were linked to problematic executive functioning in adolescents, and the latter was negatively linked to academic achievement. This study offers innovative insights by investigating relationships less explored in the scientific literature. It reveals high and significant correlations between metacognitive beliefs, maladaptive emotion regulation strategies, and trait anxiety (r > 0.500, p < 0.001) but also between these variables and both executive functioning and academic achievement. These findings offer new perspectives for research and underscore the importance of holistically examining the psychological factors related to academic success.

The Brain Imaging Data Structure (BIDS) is a community-driven specification for organizing neuroscience data and metadata with the aim to make datasets more transparent, reusable, and reproducible. Intracranial electroencephalography (iEEG) data offer a unique combination of high spatial and temporal resolution measurements of the living human brain. To improve internal (re)use and external sharing of these unique data, we present a specification for storing and sharing iEEG data: iEEG-BIDS.

Pregnancy is a state of multiple physiological adaptations. Since methylation of DNA is an epigenetic mechanism that regulates gene expression and contributes to adaptive phenotypic variations, we investigated methylation changes in maternal blood of a longitudinal cohort of pregnant women from the first trimester of gestation to the third. Interestingly, during pregnancy, we found a gain of methylation in genes involved in morphogenesis, such as ezrin, while we identified a loss of methylation in genes promoting maternal-infant bonding (AVP and PPP1R1B). Together, our results provide insights into the biological mechanisms underlying physiological adaptations during pregnancy.

Background. No device is yet available to effectively capture the attentional repercussions of hypersomnolence (HYP). The present study aimed to compare attentional performance of children with HYP, attention deficit hyperactivity disorder (ADHD), and controls using behavioral and electrophysiological (EEG) markers, and to assess their relationship with conventional sleepiness measurements. Methods. Children with HYP underwent a multiple sleep latency test (MSLT) and completed the adapted Epworth sleepiness scale (AESS). Along with age-matched children with ADHD, they were submitted to a resting EEG followed by the Bron–Lyon Attention Stability Test (BLAST). The control group only performed the BLAST. Multivariate models compared reaction time (RT), error percentage, BLAST-Intensity, BLAST-Stability, theta activity, and theta/beta ratio between groups. Correlations between these measures and conventional sleepiness measurements were conducted in children with HYP. Results. Children with HYP had lower RT and BLAST-Stability than controls but showed no significant difference in BLAST/EEG markers compared to children with ADHD. The AESS was positively correlated with the percentage of errors and negatively with BLAST-Intensity. Conclusions. Children with HYP showed impulsivity and attention fluctuations, without difference from children with ADHD for BLAST/EEG markers. The BLAST–EEG protocol could be relevant for the objective assessment of attentional fluctuations related to hypersomnolence. [ABSTRACT FROM AUTHOR]

STAT2 is a transcription factor activated by type I and III IFNs. We report 23 patients with loss-of-function variants causing autosomal recessive (AR) complete STAT2 deficiency. Both cells transfected with mutant STAT2 alleles and the patients' cells displayed impaired expression of IFN-stimulated genes and impaired control of in vitro viral infections. Clinical manifestations from early childhood onward included severe adverse reaction to live attenuated viral vaccines (LAV) and severe viral infections, particularly critical influenza pneumonia, critical COVID-19 pneumonia, and herpes simplex virus type 1 (HSV-1) encephalitis. The patients displayed various types of hyperinflammation, often triggered by viral infection or after LAV administration, which probably attested to unresolved viral infection in the absence of STAT2-dependent types I and III IFN immunity. Transcriptomic analysis revealed that circulating monocytes, neutrophils, and [CD8.sup.+] memory T cells contributed to this inflammation. Several patients died from viral infection or heart failure during a febrile illness with no identified etiology. Notably, the highest mortality occurred during early childhood. These findings show that AR complete STAT2 deficiency underlay severe viral diseases and substantially impacts survival., Introduction Human type I and III IFNs operate in almost all cell types (1, 2). Type I IFNs (IFN-[alpha]/[beta]) are thought to be secreted by most, if not all, of [...]

Abstract Background Xanthomonas oryzae pv. oryzae (Xoo) causes bacterial leaf blight, a devastating disease of rice. Among the type-3 effectors secreted by Xoo to support pathogen virulence, the Transcription Activator-Like Effector (TALE) family plays a critical role. Some TALEs are major virulence factors that activate susceptibility (S) genes, overexpression of which contributes to disease development. Host incompatibility can result from TALE-induced expression of so-called executor (E) genes leading to a strong and rapid resistance response that blocks disease development. In that context, the TALE functions as an avirulence (Avr) factor. To date no such avirulence factors have been identified in African strains of Xoo. Results With respect to the importance of TALEs in the Rice-Xoo pathosystem, we aimed at identifying those that may act as Avr factor within African Xoo. We screened 86 rice accessions, and identified 12 that were resistant to two African strains while being susceptible to a well-studied Asian strain. In a gain of function approach based on the introduction of each of the nine tal genes of the avirulent African strain MAI1 into the virulent Asian strain PXO99A, four were found to trigger resistance on specific rice accessions. Loss-of-function mutational analysis further demonstrated the avr activity of two of them, talD and talI, on the rice varieties IR64 and CT13432 respectively. Further analysis of TalI demonstrated the requirement of its activation domain for triggering resistance in CT13432. Resistance in 9 of the 12 rice accessions that were resistant against African Xoo specifically, including CT13432, could be suppressed or largely suppressed by trans-expression of the truncTALE tal2h, similarly to resistance conferred by the Xa1 gene which recognizes TALEs generally independently of their activation domain. Conclusion We identified and characterized TalD and TalI as two African Xoo TALEs with avirulence activity on IR64 and CT13432 respectively. Resistance of CT13432 against African Xoo results from the combination of two mechanisms, one relying on the TalI-mediated induction of an unknown executor gene and the other on an Xa1-like gene or allele.